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Series GSE203318 Query DataSets for GSE203318
Status Public on Oct 31, 2023
Title BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [ATAC-Seq II]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Chromatin remodeling caused by SWI/SNF (BAF) complexes is essential for regulating cell fates. Of these, BRD9, an essential component of the non-canonical BAF (ncBAF) complex, is post-transcriptionally decayed in multiple types of cancer, especially in myelodysplastic syndrome (MDS). However, how BRD9 loss or ncBAF disruption alters the HSCs' integrity remains unknown. Here, we identify that Brd9 loss enhances chromatin accessibility, promoting myeloid-lineage skewing at the expense of B cell development in vivo, followed by MDS development. Brd9 significantly colocalizes with Ctcf, whose peaks are stoichiometrically enhanced by Brd9 loss, leading to increased chromatin loops with the larger chromatin domains intact. These Ctcf-associated chromatin loops newly occur in myeloid-related genes. These data uncover the unrecognized roles of BRD9/ncBAF in the cell fate specification of HSCs via fine-tuning chromatin loops and shed light on the mechanism of ncBAF-disrupted cancer.
Overall design 1.0 x 10E3 total BM leukemic cells of Mx1-Cre Brd9fl/fl mice which transduced with MLL-AF9 cDNA transplanted via tail vein injection into lethally irradiated (two times 450 cGy) CD45.1+ recipient mice. The next day after BMT, the recipient mice received 20 mg/kg pIpC or PBS injection every other day for a total of 3 doses. 10 days after pIpC/PBS injection, the recipient mice were sacrificed for sample preparation.
Contributor(s) Nomura M, Zang W, Xiao M, Inoue D
Citation(s) 38102116
Submission date May 18, 2022
Last update date Jan 02, 2024
Contact name Masaki Nomura
Organization name Foundation for Biomedical Research and Innovation at Kobe
Street address 6-3-7 Minatojima Minamimachi, Chuo Ward
City Kobe
State/province Hyogo
ZIP/Postal code 650-0047
Country Japan
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM6166442 Ctrl_MA9_ATAC
GSM6166443 KO_MA9_ATAC
This SubSeries is part of SuperSeries:
GSE203322 BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state
BioProject PRJNA839410

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Supplementary file Size Download File type/resource
GSE203318_RAW.tar 479.8 Mb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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